Lecture 15. Sex Hormones.docx

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Cynthia Darlington

Sex Hormones 9/4/2013 3:07:00 AM Hormones as drugs:  Difficult o Bioavailability, half-life and potency  Effects depend upon age and gender  Risks associated Complete failure to produce sex hormones is RARE, but when it happens:  Modulation of gonadotropin releasing hormone (GnRH) is the optimal therapeutic strategy  Leaves the feedback mechanisms in a more “natural” state  ONLY successful if ovaries/testes are functional  Many GnRH agonists & antagonists o agonists: gonadorelin, nafarelin  Gonadorelin: o Effects deoend in method of administration:  pulsatile/continuous Fertility Drugs:  Clomiphene – Oestrogen receptor antagonist  Gonadotrophins – human recombinants LOOK UP  GnRH – synthetic, given in pulsatile fashion  Infertility: o Male:  LOW sperm count, immobile sperm, abnormal sperm  Administration of gonadotrophins may stimulate spermatogenesis and androgen release o Female:  Failure to ovulate, fallopian tube failure  Responsive to drug treatment  Clomiphene: o Oestrogen receptor antagonist  Oestrogen negatively feedbacks to decrease:  GnRH release from hypothalamus  FSH and LH release from anterior pituitary   results in INCREASED GnRH, FSH & LH o  Induces ovulation o Treats infertility due to anovulation o Twins or other multiple births common o Also used in males  Stimulates gonadotrophin release  Stimulates spermatogenesis   Gonadotrophins: o Chorionic gonadotrophin o Menotrophin  Urofollitrophin (LH removed) o Follitrophin  rhFSH o Uses:  Treats lack of ovulation in females  Treats low sperm count in males due to deficiency of GnRH  IVF In Vitro Fertilization (IVF)  3 hormones administered: o Buserelin  Nasal spray, daily from cycle day one  Suppresses ovulation o Follicle stimulating hormone  Injection every day until eggs are maturing, (around 10 days) o HGG (human chorionic gonadotrophin)  Single injection  Eggs are harvested 36 hours later  If successful: o At about 12 hours nuclei fuse, chromosomes exchange, cell division begins o Multiple births occur in 20-30% of pregnancies ERß Receptors:  Present on platelets and promote aggregation by increasing thrombin leading to increased risk of thrombosis ERα Receptors:  Cause reduction in formation of osteoclasts by inducing monocyte apoptosis  good for osteoporosis  Modulates the synthesis of plasma proteins  Required for GLUT4 expression in muscle cells  Mediate hepatic insulin sensitivity o Possible role in development of insulin resistance for both/either type of diabetes ERα and ERß:  Both involved in energy balance (mainly ERα)  CV, bone effects  Electrolyte balance / fluid homeostasis  Both present in the brain - may protect dopaminergic neurons Main Role of Estrogen (preparation for pregnancy):  Primes uterus for implantation of fertilized ovum  Stimulates uterine growth  Thickens vaginal mucosa  Thins cervical mucus production  Develops ducts in breasts Estrogen drugs: Natural Semi-synthetic Synthetic 17ß-oestradiol Ethinyloestradiol Mestranol (prodrug of (conjugated) (60x MORE POTENT ethinyloestradiol) than conjugated oestradiol) Estrogen effects:  Retention of salt & water: in pregnancy increased blood volume is need
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